MICU1 (mitochondrial calcium uptake 1) is a regulatory subunit of the mitochondrial calcium uniporter (MCU) complex that controls calcium transport across the inner mitochondrial membrane 1. In skeletal muscle, MICU1 demonstrates high calcium affinity, enabling mitochondrial calcium uptake at lower concentrations to support rapid metabolic responses and sustained ATP production during exercise 2. The protein localizes to the mitochondrial intermembrane space and functions as part of a regulatory complex alongside MICU2 and MICU3 13. Mechanistically, MICU1 maintains mitochondrial calcium homeostasis by modulating MCU activity. In endothelial cells, MICU1 prevents excessive mitochondrial calcium influx, thereby preserving sirtuin 3 (SIRT3) expression and reducing mitochondrial reactive oxygen species production 4. Reduced MICU1 expression correlates with age-associated inflammation in macrophages, as decreased mitochondrial calcium uptake amplifies cytosolic calcium oscillations and potentiates nuclear factor kappa B activation 5. Disease relevance includes myopathy with extrapyramidal signs, with MICU1 mutations identified in complex childhood-onset hyperkinetic movement disorders 6. Additionally, decreased MICU1 expression in endothelial cells covering atherosclerotic plaques associates with coronary artery disease risk 4. MICU1 emerges as both a contributor to age-related mitochondrial dysfunction and a potential therapeutic target for metabolic and vascular diseases.